Cytokines and Lymphoid Populations as Potential Biomarkers in Locally and Borderline Pancreatic Adenocarcinoma

Simple Summary PDAC remains as one of the deadliest types of cancer due to its late diagnosis, its inherent aggressiveness, and the low efficacy of routinely used treatments (from surgery or radiotherapy to systemic treatments). The search of new potential biomarkers is paramount in this context, wh...

Descripción completa

Detalles Bibliográficos
Autores: Gonzalez-Borja, I, Viudez, A, Alors-Perez, E, Goni, S, Amat, I, Ghanem, I, Pazo-Cid, R, Feliu, J, Alonso, L, Lopez, C, Arrazubi, V, Gallego, J, Perez-Sanz, J, Hernandez-Garcia, I, Vera, R, Castano, JP, Fernandez-Irigoyen, J
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p14345
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/14345
Access Level:acceso abierto
Palabra clave:pancreatic ductal adenocarcinoma (PDAC)
biomarkers
resectable disease
borderline disease
cytokines and growth factors
T lymphocytes
B lymphocytes
protein arrays
flow cytometry and immunohistochemistry
id ES_3c0df71e5949626d2f2a6dca0d4e3853
oai_identifier_str oai:fisabio.fundanetsuite.com:p14345
network_acronym_str ES
network_name_str España
repository_id_str
spelling Cytokines and Lymphoid Populations as Potential Biomarkers in Locally and Borderline Pancreatic AdenocarcinomaGonzalez-Borja, IViudez, AAlors-Perez, EGoni, SAmat, IGhanem, IPazo-Cid, RFeliu, JAlonso, LLopez, CArrazubi, VGallego, JPerez-Sanz, JHernandez-Garcia, IVera, RCastano, JPFernandez-Irigoyen, Jpancreatic ductal adenocarcinoma (PDAC)biomarkersresectable diseaseborderline diseasecytokines and growth factorsT lymphocytesB lymphocytesprotein arraysflow cytometry and immunohistochemistrySimple Summary PDAC remains as one of the deadliest types of cancer due to its late diagnosis, its inherent aggressiveness, and the low efficacy of routinely used treatments (from surgery or radiotherapy to systemic treatments). The search of new potential biomarkers is paramount in this context, where CA19-9 is still the only recommended biomarker for the management of this disease. Thus, the main goal of the present study was to assess the potential value as predictive/prognostic biomarkers of several cytokines and growth factors in serum, as well as circulating immune populations in a cohort of 64 PDAC patients. Despite its relative low incidence, PDAC is one of the most aggressive and lethal types of cancer, being currently the seventh leading cause of cancer death worldwide, with a 5-year survival rate of 10.8%. Taking into consideration the necessity to improve the prognosis of these patients, this research has been focused on the discovery of new biomarkers. For this purpose, patients with BL and resectable disease were recruited. Serum cytokines and growth factors were monitored at different time points using protein arrays. Immune cell populations were determined by flow cytometry in peripheral blood as well as by immunohistochemistry (IHC) in tumor tissues. Several cytokines were found to be differentially expressed between the study subgroups. In the BL disease setting, two different scores were proven to be independent prognostic factors for progression-free survival (PFS) (based on IL-10, MDC, MIF, and eotaxin-3) and OS (based on eotaxin-3, NT-3, FGF-9, and IP10). In the same context, CA19-9 was found to play a role as independent prognostic factor for OS. Eotaxin-3 and MDC cytokines for PFS, and eotaxin-3, NT-3, and CK beta 8-1 for OS, were shown to be predictive biomarkers for nab-paclitaxel and gemcitabine regimen. Similarly, oncostatin, BDNF, and IP10 cytokines were proven to act as predictive biomarkers regarding PFS, for FOLFIRINOX regimen. In the resectable cohort, RANTES, TIMP-1, FGF-4, and IL-10 individually differentiated patients according to their cancer-associated survival. Regarding immune cell populations, baseline high levels of circulating B lymphocytes were related to a significantly longer OS, while these levels significantly decreased as progression occurred. Similarly, baseline high levels of helper lymphocytes (CD4+), low levels of cytotoxic lymphocytes (CD8+), and a high CD4/CD8 ratio, were related to a significantly longer PFS. Finally, high levels of CD4+ and CD8+ intratumoural infiltration was associated with significantly longer PFS. In conclusion, in this study we were able to identify several prognostic and predictive biomarker candidates in patients diagnosed of resectable or BL PDAC.MDPI2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/14345CancersISSN: 20726694reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p143452026-06-11T12:45:17Z
dc.title.none.fl_str_mv Cytokines and Lymphoid Populations as Potential Biomarkers in Locally and Borderline Pancreatic Adenocarcinoma
title Cytokines and Lymphoid Populations as Potential Biomarkers in Locally and Borderline Pancreatic Adenocarcinoma
spellingShingle Cytokines and Lymphoid Populations as Potential Biomarkers in Locally and Borderline Pancreatic Adenocarcinoma
Gonzalez-Borja, I
pancreatic ductal adenocarcinoma (PDAC)
biomarkers
resectable disease
borderline disease
cytokines and growth factors
T lymphocytes
B lymphocytes
protein arrays
flow cytometry and immunohistochemistry
title_short Cytokines and Lymphoid Populations as Potential Biomarkers in Locally and Borderline Pancreatic Adenocarcinoma
title_full Cytokines and Lymphoid Populations as Potential Biomarkers in Locally and Borderline Pancreatic Adenocarcinoma
title_fullStr Cytokines and Lymphoid Populations as Potential Biomarkers in Locally and Borderline Pancreatic Adenocarcinoma
title_full_unstemmed Cytokines and Lymphoid Populations as Potential Biomarkers in Locally and Borderline Pancreatic Adenocarcinoma
title_sort Cytokines and Lymphoid Populations as Potential Biomarkers in Locally and Borderline Pancreatic Adenocarcinoma
dc.creator.none.fl_str_mv Gonzalez-Borja, I
Viudez, A
Alors-Perez, E
Goni, S
Amat, I
Ghanem, I
Pazo-Cid, R
Feliu, J
Alonso, L
Lopez, C
Arrazubi, V
Gallego, J
Perez-Sanz, J
Hernandez-Garcia, I
Vera, R
Castano, JP
Fernandez-Irigoyen, J
author Gonzalez-Borja, I
author_facet Gonzalez-Borja, I
Viudez, A
Alors-Perez, E
Goni, S
Amat, I
Ghanem, I
Pazo-Cid, R
Feliu, J
Alonso, L
Lopez, C
Arrazubi, V
Gallego, J
Perez-Sanz, J
Hernandez-Garcia, I
Vera, R
Castano, JP
Fernandez-Irigoyen, J
author_role author
author2 Viudez, A
Alors-Perez, E
Goni, S
Amat, I
Ghanem, I
Pazo-Cid, R
Feliu, J
Alonso, L
Lopez, C
Arrazubi, V
Gallego, J
Perez-Sanz, J
Hernandez-Garcia, I
Vera, R
Castano, JP
Fernandez-Irigoyen, J
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv pancreatic ductal adenocarcinoma (PDAC)
biomarkers
resectable disease
borderline disease
cytokines and growth factors
T lymphocytes
B lymphocytes
protein arrays
flow cytometry and immunohistochemistry
topic pancreatic ductal adenocarcinoma (PDAC)
biomarkers
resectable disease
borderline disease
cytokines and growth factors
T lymphocytes
B lymphocytes
protein arrays
flow cytometry and immunohistochemistry
description Simple Summary PDAC remains as one of the deadliest types of cancer due to its late diagnosis, its inherent aggressiveness, and the low efficacy of routinely used treatments (from surgery or radiotherapy to systemic treatments). The search of new potential biomarkers is paramount in this context, where CA19-9 is still the only recommended biomarker for the management of this disease. Thus, the main goal of the present study was to assess the potential value as predictive/prognostic biomarkers of several cytokines and growth factors in serum, as well as circulating immune populations in a cohort of 64 PDAC patients. Despite its relative low incidence, PDAC is one of the most aggressive and lethal types of cancer, being currently the seventh leading cause of cancer death worldwide, with a 5-year survival rate of 10.8%. Taking into consideration the necessity to improve the prognosis of these patients, this research has been focused on the discovery of new biomarkers. For this purpose, patients with BL and resectable disease were recruited. Serum cytokines and growth factors were monitored at different time points using protein arrays. Immune cell populations were determined by flow cytometry in peripheral blood as well as by immunohistochemistry (IHC) in tumor tissues. Several cytokines were found to be differentially expressed between the study subgroups. In the BL disease setting, two different scores were proven to be independent prognostic factors for progression-free survival (PFS) (based on IL-10, MDC, MIF, and eotaxin-3) and OS (based on eotaxin-3, NT-3, FGF-9, and IP10). In the same context, CA19-9 was found to play a role as independent prognostic factor for OS. Eotaxin-3 and MDC cytokines for PFS, and eotaxin-3, NT-3, and CK beta 8-1 for OS, were shown to be predictive biomarkers for nab-paclitaxel and gemcitabine regimen. Similarly, oncostatin, BDNF, and IP10 cytokines were proven to act as predictive biomarkers regarding PFS, for FOLFIRINOX regimen. In the resectable cohort, RANTES, TIMP-1, FGF-4, and IL-10 individually differentiated patients according to their cancer-associated survival. Regarding immune cell populations, baseline high levels of circulating B lymphocytes were related to a significantly longer OS, while these levels significantly decreased as progression occurred. Similarly, baseline high levels of helper lymphocytes (CD4+), low levels of cytotoxic lymphocytes (CD8+), and a high CD4/CD8 ratio, were related to a significantly longer PFS. Finally, high levels of CD4+ and CD8+ intratumoural infiltration was associated with significantly longer PFS. In conclusion, in this study we were able to identify several prognostic and predictive biomarker candidates in patients diagnosed of resectable or BL PDAC.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fisabio.portalinvestigacion.com/publicaciones/14345
url https://fisabio.portalinvestigacion.com/publicaciones/14345
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv Cancers
ISSN: 20726694
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869406345313124352
score 15.81155

Similares en LA Referencia